Publications by authors named "Thedi Ziegler"

45 Publications

Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17.

Influenza Other Respir Viruses 2020 11 30;14(6):671-677. Epub 2020 Jul 30.

Global Influenza Programme, World Health Organization, Geneva, Switzerland.

Background: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV.

Methods: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories.

Results: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs.

Conclusions: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.
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http://dx.doi.org/10.1111/irv.12771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578327PMC
November 2020

Pandemic influenza A(H1N1pdm09) vaccine induced high levels of influenza-specific IgG and IgM antibodies as analyzed by enzyme immunoassay and dual-mode multiplex microarray immunoassay methods.

Vaccine 2020 02 24;38(8):1933-1942. Epub 2020 Jan 24.

Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Turku University Hospital, Clinical Microbiology, Kiinamyllynkatu 10, 20520 Turku, Finland. Electronic address:

Influenza A viruses continue to circulate throughout the world as yearly epidemics or occasional pandemics. Influenza infections can be prevented by seasonal multivalent or monovalent pandemic vaccines. In the present study, we describe a novel multiplex microarray immunoassay (MAIA) for simultaneous measurement of virus-specific IgG and IgM antibodies using Pandemrix-vaccinated adult sera collected at day 0 and 28 and 180 days after vaccination as the study material. MAIA showed excellent correlation with a conventional enzyme immunoassay (EIA) in both IgG and IgM anti-influenza A antibodies and good correlation with hemagglutination inhibition (HI) test. Pandemrix vaccine induced 5-30 fold increases in anti-H1N1pdm09 influenza antibodies as measured by HI, EIA or MAIA. A clear increase in virus-specific IgG antibodies was found in 93-97% of vaccinees by MAIA and EIA. Virus-specific IgM antibodies were found in 90-92% of vaccinees by MAIA and EIA, respectively and IgM antibodies persisted for up to 6 months after vaccination in 55-62% of the vaccinees. Pandemic influenza vaccine induced strong anti-influenza A IgG and IgM responses that persisted several months after vaccination. MAIA was demonstrated to be an excellent method for simultaneous measurement of antiviral IgG and IgM antibodies against multiple virus antigens. Thus the method is well suitable for large scale epidemiological and vaccine immunity studies.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.022DOI Listing
February 2020

Leveraging the Global Influenza Surveillance and Response System for global respiratory syncytial virus surveillance-opportunities and challenges.

Influenza Other Respir Viruses 2020 11 24;14(6):622-629. Epub 2019 Aug 24.

Global Influenza Program, Influenza Preparedness and Response, World Health Organization, Geneva, Switzerland.

Background: Respiratory syncytial virus (RSV)-associated acute lower respiratory infection is a common cause for hospitalization and hospital deaths in young children globally. There is urgent need to generate evidence to inform immunization policies when RSV vaccines become available. The WHO piloted a RSV surveillance strategy that leverages the existing capacities of the Global Influenza Surveillance and Response System (GISRS) to better understand RSV seasonality, high-risk groups, validate case definitions, and develop laboratory and surveillance standards for RSV.

Methods: The RSV sentinel surveillance strategy was piloted in 14 countries. Patients across all age groups presenting to sentinel hospitals and clinics were screened all year-round using extended severe acute respiratory infection (SARI) and acute respiratory infection (ARI) case definitions for hospital and primary care settings, respectively. Respiratory specimens were tested for RSV at the National Influenza Centre (NIC) using standardized molecular diagnostics that had been validated by an External Quality Assurance program. The WHO FluMart data platform was adapted to receive case-based RSV data and visualize interactive visualization outputs.

Results: Laboratory standards for detecting RSV by RT-PCR were developed. A review assessed the feasibility and the low incremental costs for RSV surveillance. Several challenges were addressed related to case definitions, sampling strategies, the need to focus surveillance on young children, and the data required for burden estimation.

Conclusions: There was no evidence of any significant adverse impact on the functioning of GISRS which is primarily intended for virologic and epidemiological surveillance of influenza.
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http://dx.doi.org/10.1111/irv.12672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578328PMC
November 2020

65 years of influenza surveillance by a World Health Organization-coordinated global network.

Influenza Other Respir Viruses 2018 09 25;12(5):558-565. Epub 2018 Jun 25.

Consultant and retired affiliate of the Centers for Disease Control and Prevention, Atlanta, GA, USA.

The 1918 devastating influenza pandemic left a lasting impact on influenza experts and the public, and the importance of global influenza surveillance was soon recognized. The World Health Organization (WHO) Global Influenza Surveillance Network (GISN) was founded in 1952 and renamed to Global Influenza Surveillance and Response System in 2011 upon the adoption by the World Health Assembly, of the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits ("PIP Framework"). The importance of influenza surveillance had been recognized and promoted by experts prior to the years leading up to the establishment of WHO. In the 65 years of its existence, the Network has grown to comprise 143 National Influenza Centers recognized by WHO, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories. The Network has proven its excellence throughout these 65 years, providing detailed information on circulating seasonal influenza viruses, as well as immediate response to the influenza pandemics in 1957, 1968, and 2009, and to threats caused by animal influenza viruses and by zoonotic transmission of coronaviruses. For its central role in global public health, the Network has been highly recognized by its many partners and by international bodies. Several generations of world-renowned influenza scientists have brought the Network to where it is now and they will take it forward to the future, as influenza will remain a preeminent threat to humans and to animals.
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http://dx.doi.org/10.1111/irv.12570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086847PMC
September 2018

Improving the selection and development of influenza vaccine viruses - Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18-20 November 2015.

Vaccine 2017 02 25;35(8):1104-1109. Epub 2017 Jan 25.

Global Influenza Programme, World Health Organization (WHO), Geneva, Switzerland. Electronic address:

Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014-15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014-15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share developments and exchange views. In all areas, a renewed and strengthened emphasis was placed on developing concrete and measurable actions and identifying the key stakeholders responsible for their implementation.
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http://dx.doi.org/10.1016/j.vaccine.2017.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357705PMC
February 2017

Molecular characterization of adenoviruses among finnish military conscripts.

J Med Virol 2016 Apr 14;88(4):571-7. Epub 2015 Sep 14.

National Institute for Health and Welfare (THL), Virology Unit, Helsinki, Finland.

Although adenoviruses were identified as important respiratory pathogens many years ago, little information is available concerning the prevalence of different adenovirus serotypes, which are circulating and causing epidemics in Finnish military training centers. Over a period of five years from 2008 to 2012, 3577 respiratory specimens were collected from military conscripts presenting with symptoms compatible with acute respiratory tract infection. Upon initial testing for certain respiratory viruses by real-time PCR, 837 of these specimens were identified as adenovirus-positive. For 672 of these specimens, the serotype of the adenovirus responsible was successfully determined by DNA sequencing. Serotypes 1, 2, 3, and 4 were detected in 1, 3, 181, and 487 samples, respectively. Adenovirus epidemics were observed during each year of this study. Based on these findings, adenovirus vaccination should be considered for military conscripts in the Finnish Defence Forces.
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http://dx.doi.org/10.1002/jmv.24364DOI Listing
April 2016

Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014.

Vaccine 2015 Aug 3;33(36):4368-82. Epub 2015 Jul 3.

National Influenza Center, Helsinki, Finland.

Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes.
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http://dx.doi.org/10.1016/j.vaccine.2015.06.090DOI Listing
August 2015

Efficient replication and strong induction of innate immune responses by H9N2 avian influenza virus in human dendritic cells.

Virology 2014 Dec 25;471-473:38-48. Epub 2014 Oct 25.

Virology Unit, National Institute for Health and Welfare (THL), Mannerheimintie 166, FI-00271 Helsinki, Finland.

Avian influenza A (H9N2) viruses have occasionally been identified in humans with upper respiratory tract infections. The novel H7N9/2013 virus identified in China shows that a low pathogenic avian influenza (LPAI) virus can be highly pathogenic in humans. Therefore, it is important to understand virus-host cell interactions and immune responses triggered by LPAI viruses in humans. We found that LPAI A/Hong Kong/1073/99 (H9N2) virus replicated efficiently in human dendritic cells (DCs). The H9N2 virus induced strong IFN gene expression although with different kinetics than seasonal influenza A/Beijing/353/89 (H3N2) virus. IFN inducible antiviral proteins were produced in H9N2 virus-infected cells at the same level as in H3N2 infection. The H9N2 virus was extremely sensitive to the antiviral actions of type I IFNs. These results indicate that the avian influenza H9N2 virus is inducing a strong antiviral IFN response in human DCs.
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http://dx.doi.org/10.1016/j.virol.2014.10.002DOI Listing
December 2014

Effectiveness of pandemic and seasonal influenza vaccines in preventing laboratory-confirmed influenza in adults: a clinical cohort study during epidemic seasons 2009-2010 and 2010-2011 in Finland.

PLoS One 2014 29;9(9):e108538. Epub 2014 Sep 29.

Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.

Background: One dose of pandemic influenza vaccine Pandemrix (GlaxoSmithKline) was offered to the entire population of Finland in 2009-10. We conducted a prospective clinical cohort study to determine the vaccine effectiveness in preventing febrile laboratory-confirmed influenza infection during the influenza season 2009-10 and continued the study in 2010-11.

Methods: In total, 3,518 community dwelling adults aged 18-75 years living in Tampere city were enrolled. The participants were not assigned to any vaccination regimen, but they could participate in the study regardless of their vaccination status or intention to be vaccinated with the pandemic or seasonal influenza vaccine. They were asked to report if they received Pandemrix in 2009-10 and/or trivalent influenza vaccine in 2010-11. Vaccinations were verified from medical records. The participants were instructed to report all acute symptoms of respiratory tract infection with fever (at least 38°C) and pneumonias to the study staff. Nasal and oral swabs were obtained within 5-7 days after symptom onset and influenza-specific RNA was identified by reverse transcription polymerase chain reaction.

Results: In 2009-10, the estimated vaccine effectiveness was 81% (95%CI 30-97). However, the vaccine effectiveness could not be estimated reliably, because only persons in prioritized groups were vaccinated before/during the first pandemic wave and many participants were enrolled when they already had the symptoms of A(H1N1)pdm09 influenza infection. In 2010-11, 2,276 participants continued the follow-up. The vaccine effectiveness, adjusted for potential confounding factors was 81% (95%CI 41-96) for Pandemrix only and 88% (95%CI 63-97) for either Pandemrix or trivalent influenza vaccine 2010-11 or both, respectively.

Conclusion: Vaccination with an AS03-adjuvanted pandemic vaccine in 2009-10 was still effective in preventing A(H1N1)pdm09 influenza during the following epidemic season in 2010-11.

Trial Registration: ClinicalTrials.gov NCT01024725. NCT01206114.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108538PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180439PMC
November 2015

Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999-2012.

Clin Infect Dis 2014 Dec 19;59(11):1519-24. Epub 2014 Aug 19.

National Influenza Center, National Institute for Health and Welfare, Helsinki, Finland.

Background: Influenza B virus strains in trivalent influenza vaccines are frequently mismatched to the circulating B strains, but the population-level impact of such mismatches is unknown. We assessed the impact of vaccine mismatch on the epidemiology of influenza B during 12 recent seasonal outbreaks of influenza in Finland.

Methods: We analyzed all available nationwide data on virologically confirmed influenza infections in all age groups in Finland between 1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009-2010. We derived data on influenza infections and the circulation of different lineages of B viruses during each season from the Infectious Diseases Register and the National Influenza Center, National Institute for Health and Welfare, Finland.

Results: A total of 34 788 cases of influenza were recorded. Influenza A accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B infections were caused by viruses representing the other genetic lineage than the one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted for 10.8% of all influenza infections in the population, the proportion being highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged ≥70 years.

Conclusions: The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines.
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http://dx.doi.org/10.1093/cid/ciu664DOI Listing
December 2014

Performance characteristics of qualified cell lines for isolation and propagation of influenza viruses for vaccine manufacturing.

Vaccine 2014 Nov 24;32(48):6583-90. Epub 2014 Jun 24.

Cell culture is now available as a method for the production of influenza vaccines in addition to eggs. In accordance with currently accepted practice, viruses recommended as candidates for vaccine manufacture are isolated and propagated exclusively in hens' eggs prior to distribution to manufacturers. Candidate vaccine viruses isolated in cell culture are not available to support vaccine manufacturing in mammalian cell bioreactors so egg-derived viruses have to be used. Recently influenza A (H3N2) viruses have been difficult to isolate directly in eggs. As mitigation against this difficulty, and the possibility of no suitable egg-isolated candidate viruses being available, it is proposed to consider using mammalian cell lines for primary isolation of influenza viruses as candidates for vaccine production in egg and cell platforms. To investigate this possibility, we tested the antigenic stability of viruses isolated and propagated in cell lines qualified for influenza vaccine manufacture and subsequently investigated antigen yields of such viruses in these cell lines at pilot-scale. Twenty influenza A and B-positive, original clinical specimens were inoculated in three MDCK cell lines. The antigenicity of recovered viruses was tested by hemagglutination inhibition using ferret sera against contemporary vaccine viruses and the amino acid sequences of the hemagglutinin and neuraminidase were determined. MDCK cell lines proved to be highly sensitive for virus isolation. Compared to the virus sequenced from the original specimen, viruses passaged three times in the MDCK lines showed up to 2 amino acid changes in the hemagglutinin. Antigenic stability was also established by hemagglutination inhibition titers comparable to those of the corresponding reference virus. Viruses isolated in any of the three MDCK lines grew reasonably well but variably in three MDCK cells and in VERO cells at pilot-scale. These results indicate that influenza viruses isolated in vaccine certified cell lines may well qualify for use in vaccine production.
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http://dx.doi.org/10.1016/j.vaccine.2014.06.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915289PMC
November 2014

Decline in temperature and humidity increases the occurrence of influenza in cold climate.

Environ Health 2014 Mar 28;13(1):22. Epub 2014 Mar 28.

Institute of Health Sciences, University of Oulu, P,O, Box 5000, FI-90014 Oulu, Finland.

Background: Both temperature and humidity may independently or jointly contribute to the risk of influenza infections. We examined the relations between the level and decrease of temperature, humidity and the risk of influenza A and B virus infections in a subarctic climate.

Methods: We conducted a case-crossover study among military conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training period and identified 66 influenza A and B cases by PCR or serology. Meteorological data such as measures of average and decline in ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods, prior and after the onset were obtained.

Results: The average temperature preceding the influenza onset was -6.8 ± 5.6°C and AH 3.1 ± 1.3 g/m3. A decrease in both temperature and AH during the hazard period increased the occurrence of influenza so that a 1°C decrease in temperature and 0.5 g decrease per m3 in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR 1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was positively associated with both the average temperature [OR 1.10 per 1°C (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m3 (1.05 to 1.49)] during the hazard period prior to onset.

Conclusion: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate.
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http://dx.doi.org/10.1186/1476-069X-13-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978084PMC
March 2014

Incidence and etiology of community-acquired pneumonia in the elderly in a prospective population-based study.

Scand J Infect Dis 2014 Apr 29;46(4):250-9. Epub 2014 Jan 29.

From the National Institute for Health and Welfare , Helsinki , Finland.

Background: We conducted a prospective population-based epidemiological study to prepare a setting for documentation of the efficacy of novel vaccines against pneumococcal (Pnc) community-acquired pneumonia (CAP) in the elderly. Specific objectives were to demonstrate setting feasibility, to construct a case definition for Pnc CAP, and to estimate its incidence.

Methods: We prospectively enrolled patients with clinical and radiological findings compatible with CAP at municipal on-call clinics serving an elderly population (age ≥ 65 y) of approximately 29,500. Sputum, urine, nasopharyngeal swab (NPS), and blood samples were analyzed using diverse methods for the identification of Pnc (culture, PCR, antigen tests, serology) and of other pathogens. The following case definition for Pnc CAP was derived: encapsulated Pnc in blood culture or in high-quality sputum culture or at least 2 of the following: positive urine Pnc antigen; ≥ 2-fold increase in serum anti-PsaA or anti-CbpA antibodies; encapsulated Pnc culture or LytA PCR in either sputum or NPS.

Results: We enrolled 490 clinical CAP patients during the 2-y follow-up, 53% of all clinical CAP patients in the source population; 323 were radiologically confirmed. The incidence of radiologically confirmed CAP was 5.5/1000 person-y (95% confidence interval (CI) 4.9-6.1) and 10.5/1000 person-y when adjusted for non-captured patients. The proportion of radiologically confirmed CAP caused by Pnc was estimated at 17%; i.e. 0.95/1000 person-y (95% CI 0.7-1.2) and 1.8 when adjusted for non-captured patients.

Conclusions: We developed and documented a feasible methodology for capturing endpoints in a vaccine trial for the prevention of pneumonia. CAP incidence in the elderly population remains considerable and Streptococcus pneumoniae was one of the most commonly detected causative agents.
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http://dx.doi.org/10.3109/00365548.2013.876509DOI Listing
April 2014

Influenza C virus infection in military recruits--symptoms and clinical manifestation.

J Med Virol 2014 May 30;86(5):879-85. Epub 2013 Sep 30.

Northern Finland Laboratory Centre, Oulu, Finland.

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.
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http://dx.doi.org/10.1002/jmv.23756DOI Listing
May 2014

The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care.

J Med Virol 2013 Sep 21;85(9):1632-8. Epub 2013 Jun 21.

Valio Ltd, Helsinki, Finland.

Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses in children attending day care. In this substudy of a randomized, double-blinded, placebo-controlled 28-week intervention study, nasopharyngeal swab samples were collected, on visits to a physician due to symptoms of infection, from children receiving control milk (N = 97) and children receiving the same milk supplemented with probiotic Lactobacillus rhamnosus GG (N = 97). The presence of 14 respiratory viruses was assessed by PCR methods, and viral findings were compared with symptom prevalences in the intervention groups. Rhinovirus was identified in 28.6% of 315 swab samples, followed by respiratory syncytial virus (12.4%), parainfluenza virus 1 (12.1%), enterovirus (8.9%), influenza A(H1N1)pdm09 (7.9%), human bocavirus 1 (3.8%), parainfluenza virus 2 (3.2%), adenovirus (2.9%), and influenza A(H3N2) (0.6%). The children in the probiotic group had less days with respiratory symptoms per month than the children in the control group (6.48 [95% CI 6.28-6.68] vs. 7.19 [95% CI 6.98-7.41], P < 0.001). Probiotic intervention did not reduce significantly the occurrence of the examined respiratory viruses, or have an effect on the number of respiratory symptoms observed at the time of a viral finding. Rhinovirus, respiratory syncytial virus, and parainfluenza virus 1 were the most common respiratory viruses in symptomatic children. Children receiving Lactobacillus rhamnosus GG had fewer days with respiratory symptoms than children in the control group, although probiotic intervention was not effective in reducing the amount of viral findings or the respiratory symptoms associated with viral findings.
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http://dx.doi.org/10.1002/jmv.23623DOI Listing
September 2013

Detection method for avian influenza viruses in water.

Food Environ Virol 2012 Mar 22;4(1):26-33. Epub 2011 Dec 22.

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Recent events have shown that humans may become infected with some pathogenic avian influenza A viruses (AIV). Since soil and water, including lakes, rivers, and seashores, may be contaminated by AIV excreted by birds, effective methods are needed for monitoring water for emerging viruses. Combining water filtration with molecular methods such as PCR is a fast and effective way for detecting viruses. The objective of this study was to apply a convenient method for the detection of AIV in natural water samples. Distilled water and lake, river, and seawater were artificially contaminated with AIV (H5N3) and passed through a filter system. AIV was detected from filter membrane by real-time RT-PCR. The performance of Zetapor, SMWP, and Sartobind D5F membranes in recovering influenza viruses was first evaluated using contaminated distilled water. SWMP, which gave the highest virus recoveries, was then compared with a pre-filter combined GF/F filter membrane in a trial using natural water samples. In this study, the cellulose membrane SMWP was found to be practical for recovery of AIVs in water. Viral yields varied between 62.1 and 65.9% in distilled water and between 1 and 16.7% in natural water samples. The borosilicate glass membrane GF/F combined with pre-filter was also feasible in filtering natural water samples with viral yields from 1.98 to 7.33%. The methods described can be used for monitoring fresh and seawater samples for the presence of AIV and to determine the source of AIV transmission in an outbreak situation.
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http://dx.doi.org/10.1007/s12560-011-9075-4DOI Listing
March 2012

[Influenza viruses--a challenge for vaccinations].

Duodecim 2012 ;128(18):1919-28

Virologin yksikkö ja kansallinen influenssakeskus, Tartuntatautiseurannan ja -torjunnan osasto, Terveyden ja hyvinvoinnin Iaitos.

The clinical picture of influenza may vary from mild respiratory infection to pneumonia requiring intensive care. Annual epidemics are most commonly caused by H3N2 or H1N1 type influenza A or influenza B viruses. The population's immune protection against a new virus type is low, whereupon morbidity and mortality may be high. Vaccinations are the most important means to decrease influenza morbidity. Annual variation and quick intercontinental migration of influenza viruses, combined with the possibility of the creation of reassortant viruses, are significant challenges for the development of influenza vaccines.
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December 2012

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals.

Influenza Other Respir Viruses 2013 May 23;7(3):431-8. Epub 2012 Aug 23.

Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Helsinki, Finland.

Background: Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine-induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross-reactivity.

Objectives: Influenza vaccine-induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age-dependent responses were also analyzed.

Methods: Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009-2010 and 2010-2011. Serum samples from vaccinated volunteers, age 20-64 years, were collected before and after vaccination with AS03-adjuvanted pandemic and non-adjuvanted trivalent seasonal influenza vaccine that was given 1 year later.

Results: Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14-75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57-98%. After primary immunization, younger individuals (20-48 years) had significantly higher antibody titers against all tested viruses than older persons (49-64 years) but this difference disappeared after the seasonal booster vaccination.

Conclusions: Even a few amino acid changes in influenza A HA may compromise the vaccine-induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.
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http://dx.doi.org/10.1111/j.1750-2659.2012.00415.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779819PMC
May 2013

Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults.

Eur J Immunol 2012 Nov 15;42(11):2913-24. Epub 2012 Aug 15.

Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Paddington, London, UK.

The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naïve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.
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http://dx.doi.org/10.1002/eji.201242504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310933PMC
November 2012

Detection of influenza A viruses with a portable real-time PCR instrument.

J Virol Methods 2012 May 22;181(2):188-91. Epub 2012 Feb 22.

Centres for Military Medicine and for Biological Threat Preparedness, Tukholmankatu 8A, FI-00290 Helsinki, Finland.

Timely identification of respiratory pathogens is essential for appropriate patient care and cohorting. In order to do rapid identification-technology near the patient we utilized the field-deployable RAZOR EX-thermocycler with a reverse transcription real-time PCR assay that detects all subtypes of influenza A virus. In addition, we developed a RT PCR assay for specific detection of influenza A(H1N1)pdm09 virus. These assays amplified segments of the matrix (M)- and the hemagglutinin (HA)-gene, respectively. Detection limits of the M-gene and the influenza A(H1N1)pdm09-specific HA-gene assays were 0.15 PFU and 8.8 PFU per reaction, respectively. With 18 influenza A viruses of different subtypes and influenza B, C, and 7 other respiratory viruses the RAZOR EX and standard real-time PCR assay results were in total agreement. From 104 clinical samples identical results were obtained by both PCR methods. Additional 21 clinical samples were tested under field conditions with the RAZOR EX instrument. Results were achieved in 90 min, including 45 min for sample preparation and they were in complete agreement with those obtained by standard real-time PCR under laboratory conditions. These methods enable highly sensitive and rapid on-site diagnostics to reliably identify patients infected with influenza A, including the influenza A(H1N1)pdm09-virus.
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http://dx.doi.org/10.1016/j.jviromet.2012.02.001DOI Listing
May 2012

Single treatment with ethanol hand rub is ineffective against human rhinovirus--hand washing with soap and water removes the virus efficiently.

J Med Virol 2012 Mar;84(3):543-7

Intestinal Viruses Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland.

Ethanol-containing hand rubs are used frequently as a substitute for hand washing with water and soap. However, not all viruses are inactivated by a short term rubbing with alcohol. The capacity of a single round of instructed and controlled hand cleaning with water and soap or ethanol-containing hand rub, respectively, was tested for removal of human rhinovirus administered onto the skin of healthy volunteers on the back of the hands. Hand washing with soap and water appeared to be much more efficient for removing rhinoviruses from skin than rubbing hands with an ethanol-containing disinfectant. After washing with soap and water the virus was detected in 3/9 (33.3%) test persons from the left hand and 1/9 (11.1%) cases from the right hand, whereas the virus was detected invariably by real-time RT-PCR from both hands after cleaning with alcohol hand rub (P-value <0.01). Both substances evaluated clinically were also tested in vitro for virucidal efficacy against Human rhinovirus2 (HRV2) using a standardized assay. Both tested substances were poor within the contact time used in the hand-cleaning test. In conclusion, thorough and conventional hand washing with water and soap can clean efficiently hands contaminated with the virus responsible for an extensive share of common cold episodes.
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http://dx.doi.org/10.1002/jmv.23222DOI Listing
March 2012

Hand washing with soap and water together with behavioural recommendations prevents infections in common work environment: an open cluster-randomized trial.

Trials 2012 Jan 16;13:10. Epub 2012 Jan 16.

National Institute for Health and Welfare (THL), Department of Infectious Disease Surveillance and Control, Intestinal Viruses Unit, PO Box 30, FIN-00271 Helsinki, Finland.

Background: Hand hygiene is considered as an important means of infection control. We explored whether guided hand hygiene together with transmission-limiting behaviour reduces infection episodes and lost days of work in a common work environment in an open cluster-randomized 3-arm intervention trial.

Methods: A total of 21 clusters (683 persons) were randomized to implement hand hygiene with soap and water (257 persons), with alcohol-based hand rub (202 persons), or to serve as a control (224 persons). Participants in both intervention arms also received standardized instructions on how to limit the transmission of infections. The intervention period (16 months) included the emergence of the 2009 influenza pandemic and the subsequent national hand hygiene campaign influencing also the control arm.

Results: In the total follow-up period there was a 6.7% reduction of infection episodes in the soap-and water arm (p = 0.04). Before the onset of the anti-pandemic campaign, a statistically significant (p = 0.002) difference in the mean occurrence of infection episodes was observed between the control (6.0 per year) and the soap-and-water arm (5.0 per year) but not between the control and the alcohol-rub arm (5.6 per year). Neither intervention had a decreasing effect on absence from work.

Conclusions: We conclude that intensified hand hygiene using water and soap together with behavioural recommendations can reduce the occurrence of self-reported acute illnesses in common work environment. Surprisingly, the occurrence of reported sick leaves also increased in the soap-and water-arm.

Trial Registration: ClinicalTrials.gov: NCT00981877

Source Of Funding: The Finnish Work Environment Fund and the National Institute for Health and Welfare.
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http://dx.doi.org/10.1186/1745-6215-13-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296604PMC
January 2012

Minor changes in the hemagglutinin of influenza A(H1N1)2009 virus alter its antigenic properties.

PLoS One 2011 11;6(10):e25848. Epub 2011 Oct 11.

Viral Infections Unit, Department of Vaccines and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.

Background: The influenza A(H1N1)2009 virus has been the dominant type of influenza A virus in Finland during the 2009-2010 and 2010-2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1)2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination.

Methods/results: Based on the HA sequences of influenza A(H1N1)2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009-2010 and 2010-2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1)2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20(th) century.

Conclusions: According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1)2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1)2009 viruses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025848PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191144PMC
February 2012

Specific viruses detected in nigerian children in association with acute respiratory disease.

J Trop Med 2011 11;2011:690286. Epub 2011 Oct 11.

Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), Helsinki, Finland.

Occurrence of different viruses in acute respiratory tract infections of Nigerian children was examined. Respiratory swabs were collected from 246 children referred to hospital clinics because of acute respiratory symptoms from February through May 2009. Validated real-time RT-PCR techniques revealed nucleic acids of at least one virus group in 189 specimens (77%). Human rhinoviruses and parainfluenza viruses were present each in one third of the children. Adenoviruses, enteroviruses, human metapneumovirus, human bocavirus, and influenza C virus were also relatively common. Possibly due to their seasonal occurrence, influenza A and B virus, and respiratory syncytial virus were detected rarely. We conclude that all major groups of respiratory tract viruses are causing illness in Nigerian children.
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http://dx.doi.org/10.1155/2011/690286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191740PMC
November 2011

Validation and diagnostic application of NS and HA gene-specific real-time reverse transcription-PCR assays for detection of 2009 pandemic influenza A (H1N1) viruses in clinical specimens.

J Clin Microbiol 2011 May 2;49(5):2009-11. Epub 2011 Mar 2.

Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL),Helsinki, Finland.

Real-time reverse transcription-PCR assays specific for the nonstructural (NS) and hemagglutinin (HA) genes of the 2009 pandemic influenza A (H1N1) virus were developed and evaluated with clinical samples from infected patients. The tests are characterized by high sensitivity and specificity and performed well throughout the first year of the 2009 pandemic.
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http://dx.doi.org/10.1128/JCM.00259-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122666PMC
May 2011

Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study.

Lancet Infect Dis 2011 Jan 22;11(1):23-9. Epub 2010 Nov 22.

Department of Paediatrics, Turku University Hospital, Finland.

Background: Few prospectively collected data are available to support the effectiveness of inactivated influenza vaccines in children younger than 2 years. We aimed to establish the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in a cohort of children younger than 3 years.

Methods: In a prospective cohort study during the influenza season of 2007-08 in Turku, Finland, between Jan 14 and April 9, 2008, we assessed the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in children aged 9 months to 3 years. Our study was part of a clinical trial on antiviral treatment of influenza in children (ClinicalTrials.gov, number NCT00593502). The vaccine was given as part of the Finnish vaccination programme as a 0·5 mL injection. Children enrolled into our study through mailed announcements and local advertisements were examined every time they had fever or signs of respiratory infection. No exclusion criteria were used for enrolment. Influenza was diagnosed with viral culture, antigen detection, and RT-PCR assays of nasal swab specimens. Vaccination status of children was determined by parental report. We calculated the primary effectiveness of influenza vaccination by comparing the proportions of infections in fully vaccinated and unvaccinated children in the follow-up cohort.

Findings: We enrolled 631 children into our study with a mean age of 2·13 years (range 9-40 months). Seven (5%) of 154 fully vaccinated children and 61 (13%) of 456 unvaccinated children contracted influenza during the study (effectiveness 66%, 95% CI 29-84; p=0·003). In the subgroup of children younger than 2 years, four (4%) of 96 fully vaccinated children and 21 (12%) of 172 unvaccinated children contracted influenza (66%, 9-88, p=0·03). We were unable to record any adverse events associated with the vaccination of the children in our study.

Interpretation: Trivalent inactivated influenza vaccine was effective in preventing influenza in young children, including those younger than 2 years. Our findings suggest that influenza vaccine recommendations should be reassessed in most countries.

Funding: F Hoffmann-La Roche Ltd.
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http://dx.doi.org/10.1016/S1473-3099(10)70255-3DOI Listing
January 2011

Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland.

PLoS One 2010 Oct 20;5(10):e13329. Epub 2010 Oct 20.

Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare THL, Helsinki, Finland.

Background: In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1) virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43-48.

Methods/results: The nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2-8 and 0-5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

Conclusions: The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1) is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958116PMC
October 2010

Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial.

Clin Infect Dis 2010 Oct;51(8):887-94

Departments of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.

Background: Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness.

Methods: We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days.

Results: Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections.

Conclusions: Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.
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http://dx.doi.org/10.1086/656408DOI Listing
October 2010

STOPFLU: is it possible to reduce the number of days off in office work by improved hand-hygiene?

Trials 2010 Jun 4;11:69. Epub 2010 Jun 4.

National Institute for Health and Welfare (THL), Department of Infectious Disease Surveillance and Control, Gastrointestinal Infections Unit, Helsinki, Finland.

Background: Acute infectious diseases are major causes of short periods of days off from work, day care and school. These diseases are mainly caused by viruses and hands have a key role in their transmission. Thus, hypothetically, they can be controlled with means of intensified hand hygiene. In this study we aim to elucidate the effect of acute infectious diseases on the work contribution in common office work and study the influence of improved hand hygiene on possible reduction of infectious disease episodes and days off from work due to acute infectious diseases.

Design: The voluntary participants have been recruited from six companies in the Helsinki region. The designated 21 study clusters were identified as operationally distinct working units each containing at least 50 people. The clusters were matched and randomized based on results of a pre-trial contagion risk survey. Improved hand hygiene is being executed with guided hand-washing with soap and water in one intervention arm and with alcohol based hand rubbing disinfectant in the other. Participants in both arms have received guidance on how to avoid infections and how to implement contagion stopping habits. A control arm is acting as before regarding hand hygiene. Data collection for evaluation of the efficacy of the interventions is based on self-reporting through weekly electronic reports. The questionnaire is enquiring about possible respiratory or gastrointestinal symptoms during the preceding week, and requests a daily report of presence of symptoms and working capacity. Etiology of the symptoms is not searched for individually, but contribution of different viruses is evaluated by sentinel surveillance, where occupational health clinics located in the premises of the participating companies collect specimens from employees visiting the clinic. Common causative agents of the diseases are being searched for using real-time PCR techniques. The duration of the intervention will be 16 months. Primary endpoints of the study are the number of reported infection episodes in a cluster within a time frame of 100 reporting weeks and the number of reported sick leave episodes in a cluster within a time frame of 100 reporting weeks.

Trial Registration: ClinicalTrials.gov Identifier: NCT00821509.
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http://dx.doi.org/10.1186/1745-6215-11-69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889989PMC
June 2010